This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. A fundamental need exists to determine whether pulmonary lesions detected on a cancer patient's high-resolution CT scan are metastatic disease. While CT has extraordinary sensitivity, it lacks the specificity to make this critical distinction. The long-term goal of our research, therefore, is to develop a new tomographic imaging method to non-invasively tag and detect cancer cells in the lungs with molecular specificity and high resolution. Our approach uses hyperpolarized (HP) gas MR imaging to visualize cancer cells that have been targeted by tumor-specific functionalized Iron Oxide Nanoparticles (SPIONs). The objective of this application is to optimize this demonstrated method in mouse models of metastatic cancer, establish its theoretical and practical detection limits, and directly compare this method to micro-CT, while using histology to establish ground truth. The central hypothesis is that this new imaging method will surpass the sensitivity of CT, while adding the molecular specificity needed to distinguish metastatic from benign lesion. The focus of this particular sub-project is on the optimization of the SPION formulation to enable vascular injection of the agent without unintended accumulation in the lungs where no tumors are present. Hence, we have the following specific aims: 1) Establish a formulation and stabilization approach that enables vascular injection of LHRH-SPIONs without unintended accumulation in the capillary beds of the lungs. 2) To acquire 3He and 129Xe MRI images in control mice before and after vascular injection of LHRH-SPIONs to test for absence of accumulation 3) To obtain histopathology on these mice to further determine absence of SPION accumulation. 4) To repeat the above tests in mice that do have metastatic tumors and to observe accumulation of LHRH-SPIONs. This work represents a critical technical step to more broadly establish the approach of molecular imaging of the lung combining hyperpolarized gas MRI and targeted super-paramagnetic iron oxide nanoparticles. This work is part of an ongoing collaboration between Louisiana State University and Duke.